Effectiveness of bortezomib treatment in patients with multiple myeloma at the Clínicas Hospitalbetween 2009 and 2016. Montevideo, Uruguay
Abstract
Abstract: multiple mieloma represents the secon neoplasis in terms of frequency. It is an incurable disease, whose survival has doubled in recent years with the emergence of new drugs. Plan including bortezomib improve response, progression free survival and global survival. In Uruguay this drig is covered by the National Resources Find (FNR) since 2009. This study aims to analyse the experience of using bortezomib in patients with a diagnosis of multiple myeloma at the Clínicas Hospital.
Method: observational, retrospective and descriptive study that included all patients with a diagnosis of multiple myeloma who received bortezomib treatment in the first, second and/or third line at the Clínicas Hospital of Montevideo; Uruguay from 2009 and 2016.
Results: 36 patients received bortezomib. The most frequently used plan was cyclophosphamide-bortezomib-dexamethasone, subcutaneously administered in 54% of cases. Global response rate was 79.5% (87% in the first line, 68.8% in the second or third line). 43.6% of patients developed polineuropahty and 28.2 % cytopenia. With a median follow up of 26 months, global survival was 61% and progression free survival was 35 months, (CI 95%, 22.6-47.4).
Conclusion: bortezomib treatment achieved a good reponse rate. Neuropathy was the most frequent toxicity. Bortezomib is an effective drug and it has the adequate safety profile to treat MM in the first, second and third line.
References
(1) Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014; 15(12):e538-48. doi: 10.1016/S1470-2045(14)70442-5.
(2) Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 2003; 348(26):2609-17. doi: 10.1056/NEJMoa030288.
(3) Mateos MV, Richardson PG, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, et al. Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial. J Clin Oncol 2010; 28(13):2259-66. doi: 10.1200/JCO.2009.26.0638.
(4) Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008; 111(5):2516-20. doi: 10.1182/blood-2007-10-116129.
(5) International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 2003; 121(5):749-57.
(6) Durie BG, Harousseau JL, Miguel JS, Bladé J, Barlogie B, Anderson K, et al. International uniform response criteria for multiple myeloma. Leukemia 2006; 20(9):1467-73. doi: 10.1038/sj.leu.2404284.
(7) National Institutes of Health. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE), v.4.0. (v4.03: June 14, 2010). USA: NCI, 28 may 2009: 194 p. (NIH Publication, 09-5410).
(8) Durie BG, Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer 1975; 36(3):842-54.
(9) Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Bladé J, et al. International staging system for multiple myeloma. J Clin Oncol 2005; 23(15):3412-20. doi:10.1200/JCO.2005.04.242.
(10) Mikhael JR, Dingli D, Roy V, Reeder CB, Buadi FK, Hayman SR, et al. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines 2013. Mayo Clin Proc 2013; 88(4):360-76. doi: 10.1016/j.mayocp.2013.01.019.
(11) Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M, et al. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet 2010; 376(9758):2075-85. doi: 10.1016/S0140-6736(10)61424-9.
(12) Barlogie B, Anaissie E, van Rhee F, Haessler J, Hollmig K, Pineda-Roman M, et al. Incorporating bortezomib into upfront treatment for multiple myeloma: early results of total therapy 3. Br J Haematol 2007; 138(2):176-85. doi: 10.1111/j.1365-2141.2007.06639.x.
(13) Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, et al. Safety and efficacy of bortezomib in high-risk and elderly patients with relapsed multiple myeloma. Br J Haematol 2007; 137(5):429-35. doi: 10.1111/j.1365-2141.2007.06585.x.
(14) Moreau P, Pylypenko H, Grosicki S, Karamanesht I, Leleu X, Rekhtman G, et al. Subcutaneous versus intravenous bortezomib in patients with relapsed multiple myeloma: subanalysis of patients with renal impairment in the phase III MMY-3021 study. Haematologica 2015; 100(5):e207-10. doi: 10.3324/haematol.2014.118182.
(15) Jagannath S, Durie BG, Wolf J, Camacho E, Irwin D, Lutzky J, et al. Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma. Br J Haematol 2005; 129(6):776-83. doi: 10.1111/j.1365-2141.2005.05540.x.
(16) Mateos MV, Hernández JM, Hernández MT, Gutiérrez NC, Palomera L, Fuertes M, et al. Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study. Blood 2006; 108(7):2165-72. doi: 10.1182/blood-2006-04-019778.
(17) Kropff M, Liebisch P, Knop S, Weisel K, Wand H, Gann CN, et al. DSMM XI study: dose definition for intravenous cyclophosphamide in combination with bortezomib/dexamethasone for remission induction in patients with newly diagnosed myeloma. Ann Hematol 2009; 88(11):1125-30. doi: 10.1007/s00277-009-0726-6.
(18) Kumar S, Flinn I, Richardson PG, Hari P, Callander N, Noga SJ, et al. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood 2012; 119(19):4375-82. doi: 10.1182/blood-2011-11-395749.
(19) Mele G, Giannotta A, Pinna S, Loseto G, Coppi MR, Brocca CM, et al. Frail elderly patients with relapsed-refractory multiple myeloma: efficacy and toxicity profile of the combination of bortezomib, high-dose dexamethasone, and low-dose oral cyclophosphamide. Leuk Lymphoma 2010; 51(5):937-40. doi: 10.3109/10428191003695660.
(20) Ahn JS, Yang DH, Jung SH, Park HC, Moon JH, Sohn SK, et al. A comparison of bortezomib, cyclophosphamide, and dexamethasone (Vel-CD) chemotherapy without and with thalidomide (Vel-CTD) for the treatment of relapsed or refractory multiple myeloma. Ann Hematol 2012; 91(7):1023-30. doi: 10.1007/s00277-012-1420-7.
